Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 6 2022 12 24 646 656 Maryam Hemmatzadeh Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran AND Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Elham Ahangar Parvin Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran Alireza Ghanavatinejad Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Narges Rostami Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Mehrzad Hajaliloo Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Navid Shomali Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran AND Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Hamed Mohammadi Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran AND Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran Farhad Jadidi-Niaragh Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 2022 08 15 2022 10 08  Natural killer (NK) cells play a role in the pathogenesis of rheumatoid arthritis (RA). Upregulated levels of programmed cell death protein 1 (PD-1) is a sign of exhausted NK cells that could be regulated by microRNAs (miRNAs). In this investigation, we determined PD‑1 expression on NK cells (as a representation of NK cell exhaustion) in RA patients and evaluated if miRNAs are involved in the modulation of PD-1 expression in NK cells. Peripheral blood specimens were obtained from 40 RA patients and 20 healthy subjects. NK cells were isolated by negative selection from a pool of peripheral blood mononuclear cells. The frequency of PD-1–expressing NK cells and the expression of PD-1 on NK cells were analyzed by flow cytometry. Real-time PCR was used to measure the expression levels of PD-1 mRNA and miRNAs in the NK cells. The percentage of the PD-1–expressing NK cells and Mean fluorescence intensity (MFI) of PD-1 expression on the NK cells were significantly higher in the RA cases compared to the controls. The mRNA expression of PD-1 was significantly upregulated in NK cells from RA patients compared to healthy subjects. The expression levels of miR-28, miR-138, and miR-4717 were significantly downregulated in the NK cells from RA patients compared to the healthy group. In RA, miRNAs probably regulate the NK cell exhaustion process through driving PD-1 expression. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3628 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3628/1901